Instructions for Letram film-coated tablets 500 mg No. 30
Composition
active ingredient: levetiracetam;
1 tablet contains levetiracetam 250 mg; 500 mg; or 1000 mg;
excipients: corn starch, croscarmellose sodium, povidone, colloidal anhydrous silicon dioxide, talc, magnesium stearate;
film coating:
tablets 250 mg: Opadry II Blue 85F20694 (polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, indigo carmine (E 132));
tablets 500 mg: Opadry II Yellow 85F32004 (polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, iron oxide yellow (E 172));
tablets 1000 mg: Opadry II White 85F18422 (polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc).
Dosage form
Film-coated tablets.
Main physicochemical properties:
250 mg tablets: blue, oblong, scored, film-coated tablets, with the inscription “H” on one side and “87” on the other;
500 mg tablets: yellow, oblong, scored, film-coated tablets, with the inscription “H” on one side and “88” on the other;
1000 mg tablets: white, oblong, scored, film-coated tablets, debossed with “H” on one side and “91” on the other.
Pharmacotherapeutic group
Antiepileptic drugs. Levetiracetam.
ATX code N03A X14.
Pharmacological properties
Pharmacodynamics.
The active substance levetiracetam is a pyrrolidone derivative (S-enantiomer of α-ethyl-2-oxo-1-pyrrolidine-acetamide), which differs in chemical structure from known antiepileptic drugs.
Mechanism of action
The mechanism of action of levetiracetam is not well understood, but it is established that it differs from the mechanism of action of known antiepileptic drugs. Based on in vitro and in vivo studies, it is assumed that levetiracetam does not alter the basic characteristics of the nerve cell and normal neurotransmission.
In vitro studies have shown that levetiracetam affects intracellular Ca2+ levels by partially inhibiting current through N-type Ca2+ channels and reducing Ca2+ release from intracellular stores. It also partially reverses the inhibition of GABA- and glycine-gated currents induced by zinc and β-carbolines. In addition, levetiracetam has been shown to bind to specific sites in rodent brain tissue in in vitro studies. This binding site is synaptic vesicle protein 2A, which is involved in vesicle fusion and neurotransmitter release. Levetiracetam and related analogues display ordered binding affinity for synaptic vesicle protein 2A, which correlates with their anticonvulsant effects in an audiogenic mouse model of epilepsy. These results suggest that the interaction between levetiracetam and synaptic vesicle protein 2A contributes to the antiepileptic effect of the drug.
Pharmacodynamic effects
Levetiracetam provides protection against seizures in a wide range of partial and primary generalized seizure models in animals without causing proconvulsant effects. The main metabolite is inactive.
In humans, the activity of the drug in both partial and generalized forms of epilepsy (epileptiform manifestations/photoparoxysmal reaction) confirmed the broad spectrum of the pharmacological profile of levetiracetam.
Pharmacokinetics.
Levetiracetam is a highly soluble, permeable compound. The pharmacokinetic profile is linear with low interindividual variability. No changes in clearance are observed after multiple dosing. There is no evidence of relevant changes related to gender, race or circadian rhythm. The pharmacokinetic profile is comparable in healthy volunteers and in patients with epilepsy.
Due to complete and linear absorption, plasma concentrations can be predicted from the oral dose of levetiracetam, expressed in milligrams per kilogram (mg/kg) of body weight. Therefore, there is no need for monitoring of levetiracetam plasma concentrations.
A significant correlation between saliva and plasma concentrations was found in adults and children (plasma/saliva concentration ratio ranged from 1 to 1.7 after taking the tablets and 4 hours after taking the oral solution).
Adults and adolescents
Absorption
Levetiracetam is rapidly absorbed after oral administration. Absolute oral bioavailability is close to 100%. Peak plasma concentrations (Cmax) are reached 1.3 hours after dosing. Steady state is reached after 2 days of twice daily dosing. Cmax is typically 31 and 43 μg/mL after a single 1000 mg dose and a repeated 1000 mg dose twice daily, respectively. The extent of absorption is independent of dose and is not affected by food.
Distribution
There are no data on the distribution of the drug in human tissues. Neither levetiracetam nor its main metabolite is significantly bound to plasma proteins (the volume of distribution of levetiracetam is 0.5 to 0.7 l/kg, which is approximately equal to the total body water volume).
Levetiracetam metabolism in humans is negligible. The main metabolic pathway (24% of the dose) is enzymatic hydrolysis of the acetamide group. Hepatic cytochrome P450 isoforms are not involved in the formation of the main metabolite, ucb L057. Hydrolysis of the acetamide group has been observed in a large number of cells, including blood cells. The metabolite ucb L057 is pharmacologically inactive.
Two minor metabolites were also identified. One was formed by hydroxylation of the pyrrolidone ring (1.6% of the dose), the other by opening of the pyrrolidine ring (0.9% of the dose).
Other unidentified components accounted for only 0.6% of the dose.
No interconversion of enantiomers of levetiracetam or its major metabolite was observed in vivo.
In vitro studies have shown that levetiracetam and its main metabolite do not inhibit the activity of major cytochrome P450 isoforms (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyltransferases (UGT1A1 and UGT1A6) and epoxide hydroxylase. Levetiracetam also does not inhibit the glucuronidation of valproic acid in vitro.
In human hepatocyte culture, levetiracetam had little effect on CYP1A2, SULT1E1 or UGT1A1. Levetiracetam induced a slight induction of CYP2B6 and CYP3A4. In vitro and in vivo interaction data with oral contraceptives, digoxin and warfarin indicate no significant enzyme induction in vivo. Therefore, drug interactions with other substances or vice versa are unlikely.
Breeding
The plasma elimination half-life in adults was 7±1 hours and was independent of dose, route of administration, or repeated administration. The mean total clearance was 0.96 mL/min/kg.
The main amount of the drug, on average 95% of the dose, was excreted by the kidneys (approximately 93% of the dose was excreted within 48 hours). Only 0.3% of the dose was excreted in the feces.
The cumulative urinary excretion of levetiracetam and its major metabolite was 66% and 24% of the dose, respectively, in the first 48 hours. The renal clearance of levetiracetam and ucb L057 is 0.6 and 4.2 mL/min/kg, respectively, indicating that levetiracetam is eliminated by glomerular filtration followed by tubular reabsorption and that the major metabolite is also eliminated by active tubular secretion in addition to glomerular filtration. Levetiracetam excretion correlates with creatinine clearance.
Elderly patients
In elderly patients, the elimination half-life is increased by approximately 40% (10-11 hours). This is due to the deterioration of renal function in this population (see section "Method of administration and dosage").
Kidney dysfunction
The apparent total clearance of levetiracetam and its main metabolite correlates with creatinine clearance. Therefore, in patients with moderate to severe renal impairment, it is recommended to adjust the maintenance daily dose of levetiracetam according to creatinine clearance (see section 4.2).
In anuric patients with end-stage renal disease, the elimination half-life was approximately 25 and 3.1 hours, respectively, between and during dialysis. During a typical 4-hour dialysis session, 51% of levetiracetam was excreted.
Liver dysfunction
In patients with mild to moderate hepatic impairment, there is no significant change in the clearance of levetiracetam. In most patients with severe hepatic impairment, the clearance of levetiracetam is reduced by more than 50% due to concomitant renal impairment (see section 4.2).
Children aged 4-12 years
After a single oral dose (20 mg/kg) in epileptic children (aged 6 to 12 years), the elimination half-life of levetiracetam was 6 hours. The apparent clearance, adjusted for body weight, was approximately 30% higher than in epileptic adults.
After repeated oral administration (20 to 60 mg/kg/day) to pediatric epileptic patients (aged 4 to 12 years), levetiracetam was rapidly absorbed. Cmax was observed 0.5 to 1.0 hours after dosing. Cmax and AUC increased linearly and were dose-dependent. The elimination half-life was approximately 5 hours and the apparent total clearance was 1.1 mL/min/kg.
Indication
Monotherapy (first-choice drug) in the treatment of:
- partial seizures with or without secondary generalization in adults and adolescents aged 16 years and older with newly diagnosed epilepsy.
As an additional therapy in the treatment of:
- partial seizures with or without secondary generalization in adults and children aged 6 years and over with epilepsy;
- myoclonic seizures in adults and adolescents aged 12 years and over with juvenile myoclonic epilepsy;
- primary generalized convulsive (tonic-clonic) seizures in adults and adolescents aged 12 years and older with idiopathic generalized epilepsy.
Contraindication
Hypersensitivity to levetiracetam or to other pyrrolidone derivatives, or to any of the excipients of the drug.
Interaction with other medicinal products and other types of interactions
Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam does not affect the serum concentrations of existing antiepileptic drugs (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapeptin and primidone) and that antiepileptic drugs do not affect the pharmacokinetics of levetiracetam.
There is also no clear evidence of clinically significant drug interactions in children taking levetiracetam at doses up to 60 mg/kg/day.
A retrospective assessment of the pharmacokinetics of drug interactions in children with epilepsy (aged 4 to 17 years) confirmed that adjunctive therapy with oral levetiracetam did not affect the steady-state serum concentrations of carbamazepine and valproate when co-administered. However, the data suggest that the clearance of levetiracetam would be 20% higher in children taking enzyme-inducing antiepileptic drugs. No dose adjustment is required.
Probenecid
Probenecid (500 mg 4 times a day) blocks renal tubular secretion, inhibiting renal clearance of the main metabolite, but not of levetiracetam itself. However, the concentration of this metabolite remains low.
Methotrexate
Concomitant use of levetiracetam and methotrexate has been shown to reduce the clearance of methotrexate, leading to increased/prolonged blood concentrations of methotrexate to potentially toxic levels. Methotrexate and levetiracetam blood levels should be closely monitored in patients receiving these two drugs concomitantly.
Oral contraceptives and other pharmacokinetic interactions.
Levetiracetam at a daily dose of 1000 mg does not change the pharmacokinetics of oral contraceptives (ethinyl estradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone levels) were not changed. Levetiracetam at a daily dose of 2000 mg does not change the pharmacokinetics of digoxin and warfarin; prothrombin time values remained unchanged. Digoxin, oral contraceptives and warfarin, in turn, do not affect the pharmacokinetics of levetiracetam when used simultaneously.
Laxatives
In isolated cases, reduced efficacy of levetiracetam has been reported when the osmotic laxative macrogol was taken concomitantly with oral levetiracetam. Therefore, macrogol should not be taken orally within one hour before or one hour after taking levetiracetam.
Food and alcohol
The extent of absorption of levetiracetam is not affected by food intake, but the rate of absorption is slightly increased. There are no data on the interaction of levetiracetam with alcohol.
Application features
Stopping reception
If it is necessary to discontinue the drug, it is recommended to do so gradually (for example, for adults and adolescents weighing 50 kg or more, the dose should be reduced by 500 mg 2 times a day every 2-4 weeks; for children and adolescents weighing less than 50 kg, the single dose should be reduced by no more than 10 mg/kg 2 times a day every 2 weeks).
Kidney failure
Patients with renal impairment may require dose adjustment of levetiracetam. In patients with severe hepatic impairment, it is recommended that renal function be assessed before dose adjustment.
Acute kidney injury
The use of levetiracetam is very rarely associated with acute kidney injury, with the time to start treatment ranging from a few days to several months.
Blood laboratory tests
Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leukopenia, thrombocytopenia and pancytopenia) are usually observed initially with levetiracetam administration. A complete blood count is recommended in patients with significant weakness, fever, recurrent infections or coagulation disorders (see section 4.8).
Suicide
Cases of suicide, suicide attempts, suicidal thoughts and behavior have been reported in patients treated with antiepileptic drugs (including levetiracetam). A meta-analysis of randomized, placebo-controlled trials has shown a small increased risk of suicidal thoughts and behavior. The mechanism for this risk is not known.
Due to this risk, patients should be monitored for signs of depression and/or suicidal ideation and, if necessary, treatment should be adjusted. Patients (or their caregivers) should be advised to report any symptoms of depression and/or suicidal ideation to their physician.
Children
The tablet dosage form is not suitable for infants and children under 6 years of age.
Available data in children do not indicate an effect on growth and puberty. However, the potential effects on mental abilities, growth, endocrine system, and puberty in children remain unknown.
Use during pregnancy or breastfeeding
Postmarketing data from several prospective pregnancy registries include outcomes in over 1000 women exposed to levetiracetam as monotherapy during the first trimester of pregnancy. Overall, these data do not indicate a significant increase in the risk of congenital malformations. Therapy with multiple antiepileptic drugs is associated with a higher risk of congenital malformations than monotherapy, and monotherapy should therefore be preferred. Animal studies have shown reproductive toxicity.
Levetiracetam is not recommended during pregnancy unless clearly necessary and in women of childbearing potential not using contraception. Physiological changes during pregnancy may alter levetiracetam concentrations. A decrease in levetiracetam plasma concentrations has been observed during pregnancy. The decrease in levetiracetam concentrations is most pronounced in the third trimester (up to 60% of pre-pregnancy baseline concentrations). Appropriate clinical management of pregnant women treated with levetiracetam should be ensured. Discontinuation of antiepileptic drugs may lead to exacerbation of the disease, which may be harmful to the mother and fetus.
Breastfeeding period
Levetiracetam is excreted in human milk. Breastfeeding is therefore not recommended. However, if levetiracetam is necessary during breast-feeding, the benefits and risks of treatment should be weighed against the importance of breast-feeding.
Fertility
Animal studies have not shown any effect on fertility. The potential risk to humans is unknown as no clinical data are available.
Ability to influence reaction speed when driving vehicles or other mechanisms
Levetiracetam has minor or moderate influence on the ability to drive and use machines. Due to possible individual sensitivity, some patients may experience drowsiness, dizziness and other symptoms associated with the effects on the central nervous system, especially at the beginning of treatment or during dose increases. Therefore, such patients should be careful when engaging in activities that require increased concentration, such as driving or operating other machines. Patients are advised to refrain from driving or operating other machines until it is established that their ability to perform such activities is not impaired.
Method of administration and doses
The tablets should be taken orally with sufficient water, during or between meals. When taken orally, levetiracetam may have a bitter taste. The daily dose is divided into 2 equal doses.
Monotherapy
Monotherapy for adults and adolescents aged 16 years and over.
Monotherapy in adults and children aged 16 years and over should be initiated at the recommended dose of 500 mg/day (250 mg twice daily) with subsequent increases to the initial therapeutic dose of 1000 mg/day (to 500 mg twice daily) after 2 weeks. The dose may be increased by 500 mg/day (250 mg twice daily) every 2 weeks, depending on the clinical effect. The maximum daily dose is 3000 mg/day (1500 mg twice daily).
Children and adolescents under 16 years of age.
The safety and efficacy of Letram as monotherapy in children and adolescents under 16 years of age have not been established.
Data is missing.
Additional therapy
Adjunctive therapy for adults (≥ 18 years) and adolescents (12 to 17 years) weighing 50 kg or more.
The initial therapeutic dose is 1000 mg/day (500 mg twice daily). This is the initial dose administered on the first day of treatment. Depending on the clinical response and tolerability of the drug, the daily dose can be increased to a maximum of 3000 mg/day (1500 mg twice daily). The dose can be changed to 1000 mg/day (500 mg twice daily) every 2–4 weeks.
Adjunctive therapy for children aged 6 years and older and adolescents (aged 12 to 17 years) weighing less than 50 kg.
For infants and children under 6 years of age, it is preferable to use levetiracetam in the form of an oral solution.
As adjunctive therapy in children aged 6 years and older, the drug should be started at a dose of 10 mg/kg body weight 2 times a day. Depending on clinical response and tolerability, the dose may be increased to 30 mg/kg 2 times a day. The dose should not be increased or decreased by more than 10 mg/kg 2 times a day every 2 weeks. The lowest effective dose should be used.
Treatment of children weighing 25 kg or less should preferably be initiated with a 100 mg/ml oral solution of levetiracetam.
In children aged 6 years and over, levetiracetam oral solution should be used for doses up to 250 mg, for doses not multiples of 250 mg when the recommended dosage cannot be achieved by taking multiple tablets, and for patients who cannot swallow tablets. The lowest effective dose should be used. The starting dose for a child or adolescent weighing 25 kg should be 250 mg twice daily, with a maximum dose of 750 mg per day.
Children weighing more than 50 kg are prescribed the dosage according to the scheme given for adults.
Adjunctive therapy for infants aged 1 to 6 months.
Infants are given the drug in the form of an oral solution.
If it is necessary to stop taking the drug, it is recommended to do so gradually (for example, for adults and adolescents weighing 50 kg or more, reduce the dose by 500 mg 2 times a day every 2–4 weeks; for children and adolescents weighing less than 50 kg,
(reduce the single dose by no more than 10 mg/kg 2 times a day every 2 weeks).
Special patient groups
Elderly patients (aged 65 and over).
Dose adjustment is recommended for elderly patients with impaired renal function (see below "Renal failure").
Kidney failure.
The daily dose should be individually adjusted according to the state of renal function.
To adjust the dose for adults, use the table below.
To adjust the dose according to the table, it is necessary to determine the level of creatinine clearance (CC) in milliliters per minute (ml/min).
The creatinine clearance for adults and adolescents weighing more than 50 kg can be calculated based on serum creatinine concentration using the formula:
[140 - age (years)] × body weight (kg)
CC (ml/min) = ---------------------------------------------------- × 0.85 (for women)
72× Serum CC (mg/dL)
The CK is then adjusted for body surface area (BSA) as shown below:
CC (ml/min)
CC (ml/min/1.73 m2) = -------------------------- × 1.73
Patient's PPT (m2)
Table 1
Dosage regimen in renal insufficiency for adults and adolescents with renal insufficiency weighing more than 50 kg
| Severity of renal failure | Creatinine clearance (ml/min/1.73 m2) | Dosage regimen |
| Normal kidney function | > 80 | from 500 to 1500 mg 2 times a day |
| Easy degree | 50-79 | from 500 to 1000 2 times a day |
| Intermediate level | 30-49 | 250 to 750 mg 2 times a day |
| Severe degree | 250 to 500 mg 2 times a day | |
| End-stage (patients on dialysis(1)) | ̶ | 500 to 1000 mg once daily(2) |
(1) A loading dose of 750 mg is recommended on the first day of levetiracetam treatment.
(2) After dialysis, an additional dose of 250–500 mg is recommended.
For children with renal impairment, the dose of levetiracetam should be adjusted according to renal function, as the clearance of levetiracetam is related to renal function. This recommendation is based on a study in adult patients with renal impairment.
For children, the creatinine clearance in ml/min/1.73 m2 can be calculated from the serum creatinine level (mg/dl) using the following formula (Schwarz formula):
Height (cm) × ks
CC (ml/min) = -----------------------------------------
serum creatinine (mg/dL)
In children under 13 years of age and in adolescent girls, ks = 0.55, in adolescent boys, ks = 0.7.
Table 2
Dose adjustment recommendations for children (under 6 years of age) and adolescents with renal impairment weighing less than 50 kg
| Severity of renal failure | Creatinine clearance (ml/min/1.73 m2) | Children aged 6 years and above and adolescents weighing less than 50 kg(1) |
| Normal kidney function | > 80 | 10-30 mg/kg (0.10-0.30 ml/kg) 2 times a day |
| Easy degree | 50–79 | 10-20 mg/kg (0.10-0.20 ml/kg) 2 times a day |
| Intermediate level | 30–49 | 5-15 mg/kg (0.05-0.15 ml/kg) 2 times a day |
| Severe degree | 5-10 mg/kg (0.05-0.10 ml/kg) 2 times a day | |
| End-stage (patients on dialysis) | – | 10-20 mg/kg (0.10-0.20 ml/kg) once daily (2)(3) |
(1) For doses up to 250 mg, for doses not multiples of 250 mg, when the recommended dosage cannot be achieved by taking multiple tablets, and for patients who cannot swallow tablets, levetiracetam oral solution should be used.
(2) A loading dose of 15 mg/kg levetiracetam is recommended on the first day of treatment.
(3) After dialysis, an additional dose of 5-10 mg/kg is recommended.
Liver failure.
No dose adjustment is required for patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, creatinine clearance may not fully reflect the degree of renal impairment. Therefore, for patients with creatinine clearance <2, a 50% reduction in the daily maintenance dose is recommended.
Children.
The doctor should prescribe the most appropriate dosage form, dosage and release form, depending on age, body weight and calculated dose.
The tablet form of the drug is not recommended for use in children under 6 years of age. In this group of patients, it is preferable to use the drug in the form of an oral solution. In addition, the available tablet dosages are not suitable for the initial treatment of children weighing up to 25 kg, for patients who cannot swallow tablets, or for the use of doses up to 250 mg. In all of the above cases, it is necessary to use the drug in the form of an oral solution.
Children.
The medicine in tablet form is not recommended for use in children under 6 years of age.
Overdose
Symptoms.
Drowsiness, agitation, aggression, depression of consciousness; depression of respiratory function and coma.
After acute overdose, gastric lavage and vomiting may be performed. There is no specific antidote for levetiracetam. In case of overdose, treatment should be symptomatic and may include hemodialysis. The efficiency of levetiracetam excretion is 60%, and for the primary metabolite ̶ 74%.
Adverse reactions
The most commonly reported adverse reactions were nasopharyngitis, somnolence, headache, fatigue and dizziness. The safety profile of levetiracetam is generally similar across age groups (adults and children) in the established epilepsy indications.
List of adverse reactions.
Adverse reactions reported in clinical trials (in adults, adolescents, children and infants from 1 month of age) and during the post-marketing period are listed in the following table by system organ class and frequency. The frequency is defined as follows: very common (≥ 1/10); common (≥ 1/100,
| MedDRA organs and systems | Frequency category | | | |
| Very often | Often | Infrequently | Rarely | |
| Infections and infestations | Nasopharyngitis | Infection | | |
| From the circulatory and lymphatic system | Thrombocytopenia, leukopenia | Pancytopenia, neutropenia, agranulocytosis | | |
| On the part of the immune system | Drug reaction with eosinophilia and drug hypersensitivity syndrome (including angioedema and anaphylaxis) | | | |
| Metabolism and nutrient exchange | Anorexia | Weight gain or loss | Hyponatremia | |
| From the psyche | Depression, hostility/aggressiveness, anxiety, insomnia, nervousness/irritability | Suicide attempt, suicidal ideation, psychotic disorder, abnormal behavior, hallucinations, anger, confusion, panic attacks, emotional lability/mood swings, agitation | Suicide, personality disorder, thought disorders | |
| From the nervous system | Drowsiness, headache | Convulsions, balance disorders, dizziness, lethargy, tremor | Amnesia, memory impairment, incoordination/ataxia, paraesthesia, disturbance in attention | Choreoathetosis, dyskinesia, hyperkinesia, gait disturbance |
| From the organs of vision | Diplopia, blurred vision | | | |
| From the side of the organs of hearing and ear labyrinth | Vertigo | | | |
| Respiratory, thoracic and mediastinal disorders | Cough | | | |
| Gastrointestinal tract | Abdominal pain, diarrhea, dyspepsia, vomiting, nausea | Pancreatitis | | |
| Liver and gallbladder | Abnormal liver test results | Liver failure, hepatitis | | |
| Skin and subcutaneous tissue disorders | Rash | Alopecia, eczema, itching | Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme | |
| Musculoskeletal and connective tissue disorders | Muscle weakness, myalgia | Rhabdomyolysis and increased levels of creatine kinase (creatine phosphokinase) | | |
| General disorders and administration site conditions | Asthenia/fatigue | | | |
| Injury, poisoning and procedural complications | Injuries | | | |
Cases of encephalopathy have been observed rarely after the use of levetiracetam. These adverse effects usually occurred early in treatment (from a few days to a few months) and were reversible upon discontinuation of treatment.
Description of selected adverse reactions
The risk of anorexia is higher with concomitant use of topiramate and levetiracetam.
In several cases of alopecia, a return to normal was observed after discontinuation of levetiracetam.
In some cases of pancytopenia, bone marrow suppression has been established.
Children
It is known that a pediatric safety study evaluated the effects of levetiracetam on cognitive and neuropsychological performance in children aged 4 to 16 years with partial onset seizures. Levetiracetam was non-inferior to placebo in terms of changes from baseline on the Leiter R Attention and Memory Scale, a total score of a memory screening test in the per-protocol population. Behavioral and emotional function worsened in patients taking levetiracetam, as manifested by aggressive behavior. However, patients taking levetiracetam in a long-term, open-label study with follow-up of long-term outcomes did not experience, on average, any deterioration in behavioral and emotional function, and in particular, aggressive behavior was not worse than baseline.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister, 3 blisters in a box.
Vacation category
According to the recipe.
Producer
Hetero Labs Limited.
Location of the manufacturer and address of its place of business
Unit III, Formulation Plot No. 22 - 110 IDA, Jidimetla, Hyderabad, 500 055 Telangana, India.
Unit III, Formulation Plot No 22 - 110 IDA, Jeedimetla, Hyderabad, 500 055 Telangana, India.
